tbuckley/cabot-search huggingface dataset:
Outcomes of peritoneal metastases in mismatch repair deficient (dMMR) cancers treated with immune checkpoint inhibitors and variables associated with response.
Authors: Osama M Mosalem, Ahmed Elhariri, Nathaniel Wiest, Robin John Lester Imperial, Mohamad B. Sonbol, Zhaohui Jin, Jeremy Clifton Jones, Jason S. Starr
Journal: Journal of Clinical Oncology (2023)

e14576 Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many solid malignancies. ICI appears particularly effective when tumors exhibit high microsatellite instability (MSI-H) and/or mismatch repair deficient (dMMR) status. Although the response is typically quite good in this setting, there are scenarios where benefit is less than anticipated. In this study, we aimed to explore the efficacy of ICIs in patients with MSI-H/dMMR cancers with peritoneal metastasis (PM). Methods: We conducted a retrospective chart review to identify patients (pts) with PM from primary MSI-H/dMMR cancers treated with immunotherapy between 2010 and 2022 at Mayo Clinic. Data was collected to include pt demographics, tumor characteristics, pathology, tumor markers, imaging, mutational profile, and previous and subsequent treatments. The primary endpoint was disease control rate (DCR), defined as objective response rate (RECIST v1.1 criteria) or stable disease. Results: Forty-six pts with MSI-H/dMMR and PM treated with ICIs. Most of our cohort were female (61%) with a median age at diagnosis of 61 years. Colorectal cancer was the most common primary site (69.6%), followed by endometrial (6.5%). Most pts received treatment with PD-1 antibodies as second-line therapy following systemic chemotherapy. DCR of the PM was 71.6 % (n= 13 PR, 9 CR, and 9 SD), with a median duration of response of 12.6 months. Thirteen pts (28.4%) had progressive peritoneal disease on ICI with a median PFS of 2.2 months. Ascites was a poor prognosticator and predicted a lack of benefit from ICI (HR 6.6, 95% CI=2.24-19.9, p= 0.006). Mucinous and signet ring histology were common in pts with peritoneal progression (61.5%); however, this was not statistically significant (HR=1.6; 95%CI= 0.4383 to 3.899, p 0.5). Multivariate analysis for the presence or absence of BRAF and/or RAS mutations was not statistically significant in predicting response. Neither was the specific MMR gene mutation(i.e., MLH1 or PMS2). Interestingly, discordant responses between the peritoneum and other sites of metastasis to immunotherapy were seen in 13 pts (28.4%), primarily as primary peritoneal progression compared to other tumor sites. Conclusions: In our cohort, the DCR of metastatic peritoneal disease in MSI-H/dMMR tumors was approximately 71%. The presence of ascites was identified as a poor prognosticator in this setting and was associated with a lack of response/benefit from ICIs. Histologic subtype (i.e., mucinous/signet ring) did not show statistical significance in predicting ICI response. The subpopulation with discordant response to ICI suggests that peritoneal immunobiology may differ from other sites. Further research on immunotherapy response in the peritoneum is needed for this special subset of pts.
Health insurance continuity and survival among children, adolescents, and young adults with blood cancer: An analysis based on SEER-Medicaid data.
Authors: Xu Ji, Elyse Xinyue Zhang, Shasha Bai, Wendy Stock, Robin Yabroff, Ann C. Mertens, Sharon M. Castellino
Journal: Journal of Clinical Oncology (2023)

6504 Background: Many previously uninsured patients do not receive Medicaid coverage until the point of, or after, cancer diagnosis, which may delay access to life-saving therapies. We examined whether continuous Medicaid coverage prior to diagnosis (vs. gaining Medicaid at, or after, diagnosis) provides a survival benefit in children and adolescents/young adults (AYAs) newly diagnosed with blood cancer. Methods: Using the linked SEER cancer registry-Medicaid enrollment data, we assessed coverage during the six months prior to, the month of, and the six months after cancer diagnosis (13-month window) in 29,873 children and AYAs (aged 0-39 years) diagnosed with blood cancer in 2006-2013. To measure insurance continuity, we categorized patients who had: (1) continuous Medicaid (enrolled for ≥6 months prior to through diagnosis), (2) newly gained Medicaid at/after diagnosis (enrollment only at or ≤6 months after diagnosis), (3) other patterns of noncontinuous Medicaid, (4) private insurance, (5) other insurance, or (6) uninsured/unknown insurance. The last three groups contain patients in SEER not linked to Medicaid enrollment data; these patients’ insurance at diagnosis was available in SEER. Kaplan-Meier (KM) survival curve of 5-year overall survival was stratified by insurance continuity category. Associations between insurance continuity and survival were examined using Cox proportional hazard models, for all blood cancers combined and by cancer type (leukemia, lymphoma, myeloma). Models also adjusted for age, sex, race/ethnicity, rurality, neighborhood socioeconomic status, and diagnosis year. Results: Of our sample, 44.1% had private insurance, followed by Medicaid (28.3%), other insurance (9.6%), and no insurance (3.9%) or unknown insurance (14.1%). Of Medicaid-insured patients, 44.9% had continuous Medicaid, 38.9% gained Medicaid at/after diagnosis, and 16.2% experienced other noncontinuous patterns. The KM-estimated 5-year survival probability was 89.3% for privately insured patients, followed by other insurance (88.1%), continuous Medicaid (78.2%), other patterns of noncontinuous Medicaid (74.3%), and newly gained Medicaid at/after diagnosis (70.6%; p&lt;0.001). In multivariable analysis, patients who newly gained Medicaid at/after diagnosis had a hazard ratio (HR) for death of 2.63 (95%CI=2.42-2.87), whereas patients with continuous Medicaid and those with other noncontinuous patterns had HRs of 2.08 (95%CI=1.90-2.28) and 2.31 (95%CI=2.04-2.60), respectively, compared to privately insured patients. This finding persisted across blood cancer types. Conclusions: Less than half of Medicaid-insured children and AYAs with blood cancer had continuous insurance coverage prior to and following cancer diagnosis. Lacking continuous Medicaid coverage was associated with inferior survival.
The distribution of HPV subtype in vulvar intraepithelial neoplasia and the association with recurrent VIN and vulva cancer in Taiwan.
Authors: MIN-Jie Liao, Chyong-Huey Lai
Journal: Journal of Clinical Oncology (2023)

e17635 Background: Vulvar intraepithelial neoplasia (VIN) is a precursor lesion of vulvar cancer. Human papillomavirus (HPV) is causative for part of VIN lesions. This retrospective study aimed to investigate HPV distribution in patients with vulvar intraepithelial neoplasia (VIN) and the factor associated with the recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+), high-grade vaginal intraepithelial neoplasia (VAIN) , cervical intraepithelial neoplasia(CIN) or progression to vulvar cancer. Methods: We retrospectively analyzed patients who diagnosed as vulvar squamous intraepithelial lesions between 1990 and 2014 in our institution. All the diagnoses and classifications were confirmed by two pathologists in 2015 ISSVD terminology. HPV DNA was extracted from formalin-fixed and paraffin-embedded samples. SPF1/GP6+ polymerase chain reaction (PCR) followed by HPV Blot and E6 type-specific PCR were performed. Results: Ninety-eight VIN patients were included in our analysis. Ninety-three percent were positive for HPV and HPV16 (43.9%), HPV6 (11.38%), HPV11 (8.94%), and HPV58 (4.88%) were the most prevalent types. Patients with positive HPV were diagnosed younger than those with negative results (43.0 years vs. 61.1 years, P = 0.049). In 15 patients who with recurrent VIN (n = 11) or progression to vulvar cancer (n = 4), had positive HPV. All 4 patients who had progression to cancer were positive for HPV16 in their initial VINs. High risk type HPV infection, positive HPV16, and positive alpha-9 types are significant risk factors for recurrent VIN and progression to cancer. Conclusions: Positive HPV was detected in 92.8% of VINs and was related to younger age at diagnosis. HPV16 was the most prevalent type and was significantly related to recurrence/ progression. Other significant risk factors for recurrent VIN or progression to cancer were high-risk HPV and alpha-9 types. Closely monitor of those patients with risk factors was indicated for early detection and treatment of recurrent VIN and vulvar cancer.
Circulating tumor DNA guided therapeutic strategies for colorectal cancer patients with multiple small pulmonary-limited nodules: An open-label, prospective, phase II cohort study.
Authors: Jinjia Chang, Wenhua Li, Qijie Jian, Fei Pang, Feng Li, Kai Wang, Junjie Peng
Journal: Journal of Clinical Oncology (2023)

e15645 Background: The clinical diagnosis and treatment of small pulmonary nodules (suspected to be lung metastases) in advanced colorectal cancer (CRC) patients remain controversy. Previous studies have shown that tumor-informed circulating tumor DNA (ctDNA) testing with blood sample can sensitively detect recurrence or metastasis of CRC patients. This study was designed to explore the clinical value of tumor-informed ctDNA test in metastatic CRC patients with small pulmonary-limited nodules. We aimed to identify the low-risk patients for de-escalation therapy, as well as high-risk patients with no evidence of disease (NED) for escalation therapy. Methods: This is an ongoing, open-label, prospective and phase II cohort study (NCT 05495672). According to the longest diameter of the pulmonary nodule, patients were divided into two cohorts: Cohort 1(0-1cm) and Cohort 2 (1-2cm). Tumor-informed ctDNA test (OriMIRACLE S) would be performed every three months until progression or 2 years. The treatment strategy of each patient is decided by a multidisciplinary team depending on ctDNA and lung CT scan results. In general, negative minimal residual disease (MRD) patients will receive only regular follow-up. Patients with positive MRD will receive intensive examination and local treatments for pulmonary nodules such as surgery, radio frequency ablation or stereotactic body radiotherapy combined with or without systemic therapeutic treatment, aiming to achieve NED or cure. Results: From June 2022 to December 2022, a total of 26 patients were screened in the group, one patient was eliminated (with extrapulmonary metastasis), and a total of 25 patients were successfully enrolled. At present, 1 patient died (by acute intestinal perforation), 4 patients were excluded from the group (with the emergence of extrapulmonary metastasis), and a total of 20 patients were in the group. The positive rate of MRD in baseline were 4/11(36.4%) for Cohort 1 and 10/14 (71.4%) for Cohort 2, respectively. Notably, in Cohort 1, 3 of 4 patients with positive MRD at baseline were examined extrapulmonary metastasis during the follow-up examination. Conclusions: Our preliminary results suggested that the positive rate of MRD were higher in Cohort 2 than Cohort 1. Patients with pulmonary nodule less than 1 cm tended to develop extrapulmonary metastasis if baseline MRD was positive. In such circumstances, more intensive follow-up examination is suggested to prevent early disease progression. Clinical trial information: NCT05495672 .
FDA analysis of treatment efficacy based on etiology of hepatocellular carcinoma.
Authors: May Tun Saung, Jiaxin Fan, Joyce Cheng, Yuan-Li Shen, Sandra J. Casak, Steven Lemery, Lola A. Fashoyin-Aje
Journal: Journal of Clinical Oncology (2023)

4117 Background: Retrospective analyses of trial-level data report that etiology of hepatocellular carcinoma (HCC) (e.g., viral versus [vs.] non-viral) may influence efficacy of systemic therapies used in advanced HCC. FDA conducted an analysis of 9 randomized controlled trials (RCTs; n=5,417) to assess treatment effects based on drug class, treatment line, and HCC etiology. Methods: FDA conducted a retrospective, exploratory analysis of 3 RCTs comparing first line (1L) treatment with anti-programmed cell death (ligand)-1-containing regimens (αPD-[L]1) to single-agent anti-vascular endothelial growth factor therapy (αVEGF), and 6 RCTs comparing second line (2L) treatment consisting of αPD-(L)1 or αVEGF to placebo. For each line of treatment (1L or 2L), meta-analyses of overall survival (OS) were performed for the overall treatment effect and by disease etiology, viral (hepatitis B [HBV], or hepatitis C [HCV]) vs. non-viral. Subgroup analyses were performed to investigate the confounding effect of subsequent therapy (yes vs. no) and region (Asian vs. non-Asian) on etiology. Trial-level hazard ratios (HRs) and 95% confidence intervals (CI) were mostly calculated using patient-level data submitted to FDA. Pooled HRs and CIs were calculated using a random-effects model. Results: While 1L αPD-(L)1 improved OS compared to 1L αVEGF in the overall population (HR [95% CI]: 0.8 [0.73, 0.88]), treatment effects were comparable for viral (HR [95% CI]: 0.75 [0.6, 0.92]; n=1,435) and non-viral (HR [95% CI]: 0.83 [0.72, 0.95]; n=979) subgroup analyses, and not influenced by subsequent therapy or region. Analyses based on specific viral infection (i.e., HBV or HCV), showed that improvement in OS for αPD-(L)1 vs. αVEGF appeared larger for HBV (HR [95% CI]: 0.7 [0.59, 0.82]; n=833) compared to HCV (HR [95% CI]: 0.83 [0.6, 1.16]; n=602). Treatment effects were also comparable in 2L for different etiologies for both αPD-(L)1 (HR [95% CI] for viral: 0.76 [0.62, 0.93]; n=529 and non-viral: 0.85 [0.65, 1.11]; n=337) and αVEGF (HR [95% CI] for viral: 0.79 [0.69, 0.9]; n=1,288 and non-viral: 0.74 [0.63, 0.88]; n=849), and not influenced by subsequent therapy. Nonetheless, compared to placebo, αPD-(L)1 had a larger treatment effect with HBV (HR [95% CI]: 0.69 [0.5, 0.94]; n=459) compared to non-viral etiologies. Conclusions: The results did not demonstrate that etiology of HCC was predictive of OS for both treatment classes based on retrospective, exploratory meta-analyses of 9 RCTs; however, the treatment effects may be more pronounced in patients with HBV who received αPD-(L)1 as 1L or 2L. Uncertainty remains regarding subgroup treatment effects given limited number of trials in the analyses (mostly leading to approvals), overlapping CIs, number of patients in some subgroups, retrospective nature, and exclusion of trials with inadequate data regarding etiology of HCC.
Real-world safety and effectiveness of radium-223 (<sup>223</sup>Ra) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated in the US: The non-interventional REASSURE study.
Authors: Daniel Y. Song, Saby George, Shawn Zimberg, Luke T. Nordquist, Jeffrey Tomaszewski, Peter S Conti, Jeffrey Meltzer, Frank Verholen, Anja Schmall, Celestia S. Higano, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2023)

5050 Background: 223 Ra improved overall survival (OS) and quality of life and demonstrated a favorable safety profile in pts with mCRPC in the phase 3 ALSYMPCA trial. REASSURE (NCT02141438) is a global, prospective, single-arm, observational study of 223 Ra use in pts with mCRPC and bone metastases in routine clinical practice. Here, we present clinical outcomes from the second planned interim analysis of REASSURE for pts treated in the US. Methods: This analysis included pts with confirmed mCRPC with bone metastases scheduled to receive 223 Ra in the US. All pts received ≥1 dose of 223 Ra. Primary endpoints are short- and long-term safety, including incidence of bone marrow suppression and second primary malignancies (SPM). Secondary endpoints included OS and pt-reported pain (Brief Pain Inventory – Short Form [BPI–SF] scores). A clinically meaningful pain response was defined as a decrease from baseline of ≥2 points in BPI-SF worst pain item. Results: Pts were enrolled from 2014–2017. Overall, 498 pts were included in this analysis. At the data cut-off (20 March 2019), the median duration of observation was 11.9 months (0.4–41.3). Most pts (81%) had bone metastases only; 69% of pts received 5–6 223 Ra injections. Overall, 77% of pts had received ≥1 prior life-prolonging therapies: abiraterone (45%), enzalutamide (48%), docetaxel (25%), cabazitaxel (6%), or sipuleucel-T (24%). Concomitant enzalutamide was received by 31% of pts, and 47% received concomitant bone health agents. After 223 Ra, 31% of pts received ≥1 life prolonging therapies. During treatment, 208/358 (58%) pts with a baseline BPI-SF ≥2 had a clinically meaningful pain response. Any-grade and grade ≥3 drug-related treatment-emergent adverse events (TEAEs) occurred in 32% and 10% of pts, respectively. Drug-related TEAEs resulted in 223 Ra discontinuation in 4% of pts. Treatment-emergent and drug-related serious AEs (SAEs) occurred in 21% and 6% of pts, respectively. The most common (&gt;5% of pts) any-grade drug-related TEAEs were diarrhea (10%), fatigue (9%), anemia (8%) and nausea (7%). Overall, 4% of pts had fractures; 2% of pts developed bone disorders. Eleven SPMs occurred in 10 pts (2%). In total, 60% of pts died during study follow-up. Median OS was 17.8 months (95% CI 15.6–19.4). Conclusions: Within the current treatment landscape in routine clinical practice in the US, median OS after 223 Ra treatment was close to 18 months. A majority of pts completed 5–6 223 Ra injections. The known safety profile of 223 Ra was confirmed with no new safety signals. Over half of pts with pain at baseline had a clinically meaningful pain response during 223 Ra treatment. Clinical trial information: NCT02141438 .
Tumor lysis syndrome in solid tumors: A retrospective cohort study of the National Inpatient Sample from 2016 to 2019.
Authors: Akshit Chitkara, Akshita Khosla, Fnu Anamika, Kavin Raj, Jean-marie Koka, Bhuvaneswari Ramaswamy
Journal: Journal of Clinical Oncology (2023)

6594 Background: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. Patients with a rapidly proliferating tumor or high tumor burden after cytotoxic chemotherapy, predominantly in hematologic malignancies, are at increased risk of TLS. The advancement in therapeutic strategies of oncology in the past few decades has expanded the spectrum of malignancies associated with TLS. A dearth of literature on the incidence of TLS in various solid malignancies exists. Using the National Inpatient Sample (NIS) data, this study aims to highlight the solid malignancies at risk of TLS, highlight the demographic factors, and draw a comparison with that in hematological malignancies. Methods: The NIS 2016-2019 dataset was analyzed utilizing univariate and multivariate logistic regression analysis for the predictors of TLS (P &lt;0.05). StataCorp. 2021. Release 17. College Station, TX: StataCorp LLC, BE version with Stata’s svy command, and appropriate weights, were used to perform the analysis. The overall fit was analyzed using Receiver Operative Curves (ROC), and sensitivity analysis was analyzed using the e-value package. Results: From 2016-2019, a total of 51,385 (48,917-53,853) hospitalizations had an incidence of TLS. We included 16,249 cases of TLS in patients treated for the ten most common malignancies in the US. We found that older age, male sex, and black race were associated with higher odds of TLS. It was reported highest in large hospitals and urban non-teaching hospitals. The regional distribution of the TLS suggests the highest odds in the Western region. The odds of getting TLS were highest among Leukemias and Lymphomas, respectively. Among solid tumors, the odds of getting TLS were highest in uterine cancer patients, followed by lung, breast, pancreatic, and liver cancer among the top five. (Table). Conclusions: In this study, we conclude that solid tumors, mainly uterine, followed by lung and breast, have significantly higher odds of TLS, more so in larger or non-teaching hospitals. There is a need to establish specific management guidelines to prevent these TLS cases that will improve the morbidity and mortality associated with TLS and help build more cost-effective treatment regimens. [Table: see text]
Safety and efficacy of allogeneic natural killer cells in combination with pembrolizumab in patients with chemotherapy-refractory biliary tract cancer: A multicenter open-label phase 1/2a trial.
Authors: Galam Leem, Sung Ill Jang, Jae-Hee Cho, Jung Hyun Jo, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Da-Kyung Yoo, Hyo-Cheon Cheon, Jae-Eun Kim, Kyeong-Pill Lim, In-Hye Jung, Jung-Min Im, Yong Yoon Chung, Seung Woo Park
Journal: Journal of Clinical Oncology (2023)

4080 Background: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab, in the treatment of advanced biliary tract cancer to determine the safety and tolerability (phase 1), and the efficacy and safety (phase 2a). Methods: Forty patients (phase 1, n=6; phase 2a, n=34) were enrolled between December 2019 and June 2021. The patients were inoperable and no further conventional chemotherapy was anticipated after finishing at least one chemotherapy. The patients received 3x10 6 NK cells/kg of highly activated allogeneic NK cells (“SMT-NK”) on weeks 1 and 2 and 200 mg of pembrolizumab (Keytruda) on week 1. No treatment was given in week 3. This 3-week schedule (1 cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal of consent, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles. Results: In phase 1, 4 patients (66.7%) experienced 7 AEs, but no severe AEs directly related to the combination of the two drugs was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥ grade 3) were reported in 16 patients (47.1%). No dose limiting toxicity was reported. The overall response rate (ORR) was 17.4% in the full-analysis set and 50.0% in the per-protocol set. Conclusions: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer. A multi-center, randomized, placebo-controlled, open-label, phase 2b clinical trials to evaluate the antitumor activity of combination therapy of SMT-NKs and pembrolizumab versus pembrolizumab monotherapy in patients with advanced biliary tract cancer is now ongoing with the aim of enrolling 128 patients (ClinicalTrials.gov identifier: NCT05429697). To date, 38 patients have been enrolled and randomly assigned to each group. Within the median follow up period of 5.3 months, the disease control rate (DCR, complete response + partial response) was 27.2% in the combination therapy of SMT-NKs and pembrolizumab group, and 7.1% in the pembrolizumab monotherapy group. The ORR was 54.5% in the combination therapy group and 42.9% in the monotherapy group. So far, no severe drug-related AEs was reported. Clinical trial information: NCT03937895 .